Chromatin dependencies in cancer and inflammation
Abstract
Multiple cell-signalling pathways converge on chromatin to induce gene expression programmes. The inducible transcriptional programmes that are established as a result of inflammatory or oncogenic signals are controlled by shared chromatin regulators. Therapeutic targeting of such chromatin dependencies has proved effective for controlling tumorigenesis and for preventing immunopathologies that are driven by overt inflammation. In this Review, we discuss how chromatin dependencies are established to regulate the expression of key oncogenes and inflammation-promoting genes and how a better mechanistic understanding of such chromatin dependencies can be leveraged to improve the magnitude, timing, duration and selectivity of cell responses with the aim of minimizing unwanted cellular and systemic effects. Recently, exciting progress has been made in cancer immunotherapy and in the development of drugs that target chromatin regulators. We discuss recent advances in clinical trials and the challenge of combining immune-cell-based therapies and epigenetic therapies to improve human health.
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Enhanced tumour interferon signalling is further augmented following combination of DNMT inhibitors with HDAC inhibitors.
“This enhanced tumour interferon signalling is further augmented following combination of DNMT inhibitors with histone deacetylase (HDAC) inhibitors”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [194]
In preclinical studies, DNMT and HDAC inhibitors induced intra-tumoural T-cell infiltration and augmented the response to immune checkpoint inhibitors.
“in preclinical studies these epigenetic agents induced intra-tumoural T-cell infiltration and augmented the response to immune checkpoint inhibitors 194,195 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [194]
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The roles of DNA, RNA and histone methylation in ageing and cancer
Michalak, E. M., Burr, M. L., Bannister, A. J., & Dawson, M. A. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0143-1 · Cited by 549 · see citing works
- Authors
- Marazzi, I., Greenbaum, B. D., Low, D. H. P., & Guccione, E.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Tisch Cancer Institute (US)
- Agency for Science, Technology and Research (SG)
- Corresponding author
- Marazzi, Ivan
- Guccione, Ernesto
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2017-11-29
- Volume
- 19
- Issue
- 4
- Pages
- 245-261
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- OpenAlex
- W2768873001
- Cited by
- 80
- References
- 20
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 8 · 2023: 13 · 2022: 18 · 2021: 11 · 2020: 10 · 2019: 8 · 2018: 5 · 2017: 1
- FWCI
- 0.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- chromatin regulators, cancer, inflammation, oncogenes, epigenetic therapy, cancer immunotherapy, combination therapy, carcinogenesis, immunopathology, cell signalling pathways, transcriptional programs
- MeSH terms
- Animals, Chromatin, Humans, Inflammation, Models, Genetic, Neoplasms, Transcription Factors, Genetic Therapy, Signal Transduction, Gene Expression, Chromatin Assembly and Disassembly, Epigenesis, Genetic, Carcinogenesis
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